基于NOD2/RIP2轴介导MAPK/NF-κB信号通路探讨黄蜀葵花总黄酮治疗克罗恩病的作用及其机制

克罗恩病（CD）是临床难治性疾病之一。研究表明，NOD2/RIP2轴通过介导MAPK/NF-κB信号通路调控炎症细胞因子的释放是CD发生的关键机制和重要的治疗靶点。我们前期研究显示，黄蜀葵花及其主要成分黄蜀葵花总黄酮能够显著改善CD模型动物的肠道炎症，抑制TNF-α、INF-γ等促炎因子的释放，下调p-p38和NF-κBp65的表达，提示调节MAPK/NF-κB信号通路的过度表达及其上游的NOD2/RIP2轴可能是黄蜀葵花总黄酮治疗CD的潜在分子机制。本研究拟从整体动物和细胞水平，运用ELISA、RT-PCR、Western Blot、免疫荧光等技术，观察黄蜀葵花总黄酮对炎症相关细胞因子、MAPK/NF-κB信号通路以及NOD2/RIP2轴表达的影响，诠释黄蜀葵花总黄酮治疗CD的作用机制，为中医药治疗CD提供新的思路和依据。

Crohn’s disease(CD) is one of the clinical refractory diseases. NOD2/RIP2 axis regulates the production of pro-inflammatory cytokines through mediating MAPK/NF-κB signaling pathways,which play key role in the pathogenesis and therapeutic target of CD. Our preliminary studies showed that Abelmoschus manihot (L.) Medicus and its main component total flavone of Abelmoschus manihot (L.) Medicus(TFA) attenuated the colitis of experimental mice, reduced the pro-inflammatory cytokines TNF-α、INF-γ secretion, and down-regulated the expression of p-p38 and NF-κBp65. These results indicate that regulating the overexpression of MAPK/NF-κB signaling pathways and its upstream NOD2/RIP2 axis are potential molecular mechanisms of TFA in the treatment of CD. In order to evaluate the influence of TFA in vivo and in vitro, pro-inflammatory cytokines, expression of MAPK/NF-κB signaling pathways and NOD2/RIP2 axis are detected by ELISA, RT-PCR, Western Blot, Immunofluorescence and other techniques in this study. The aim of this study is to elucidate the mechanism of TFA in the treatment of CD, and expect to provide new ideals and evidences for treatment of CD with Chinese medicine.